Photo of Bradley E. Bernstein,  MD, PhD

Bradley E. Bernstein, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-6906
Fax: (617) 643-3566


bernstein.bradley@mgh.harvard.edu

Bradley E. Bernstein, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Pathologist , Pathology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Professor of Pathology at Harvard Medical School, Early Career Scientist at Howard Hughes Medical Institute and Senior Associate Member at the Broad Institute. Laboratory in the Richard B. Simches Research Building at Massachusetts General Hospital, part of Experimental Pathology and the Center of Systems Biology with research focused on chromatin and epigenetic regulation in normal and malignant stem cells. The laboratory applies high-throughput genomic technologies to study the role of chromatin in the regulation of cell fates, functional phenotypes and drug sensitivity. The group has introduced new technologies for mapping chromatin structure genome-wide and for locus-specific editing of chromatin modifications. Notable biological findings include the identification of alternative types of large-scale chromatin structures, or ‘domains’, that maintain gene activity, gene repression or gene potential under specific cellular contexts. For example, in differentiated cells, chromatin domains marked by either ‘active’ or ‘repressive’ histone modifications maintain expression or repression of key developmental genes. However, in pluripotent ES cells, ‘bivalent’ domains enriched for both active and repressive modifications keep developmental genes poised for subsequent activation. Current projects in the lab are focused on understanding the structures, functions and mechanisms of bivalent' domains and other chromatin states in developing stem cells. Towards this end we are deploying new technologies for profiling chromatin at single molecule and single cell resolution, and for global and locus-specific perturbation of chromatin structure. Analogous approaches are now being applied to characterize aberrant chromatin states and regulatory circuits that underlie malignant phenotypes and drug resistance in tumor models, including glioblastoma, leukemia and other cancers.

Publications

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  • , Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature 2015; 518:317-30. PubMed
  • Ziller MJ, Edri R, Yaffe Y, Donaghey J, Pop R, Mallard W, Issner R, Gifford CA, Goren A, Xing J, Gu H, Cacchiarelli D, Tsankov AM, Epstein C, Rinn JL, Mikkelsen TS, Kohlbacher O, Gnirke A, Bernstein BE, Elkabetz Y, Meissner A. Dissecting neural differentiation regulatory networks through epigenetic footprinting. Nature 2015; 518:355-9. PubMed
  • Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2015; 518:337-43. PubMed
  • Rotem A, Ram O, Shoresh N, Sperling RA, Schnall-Levin M, Zhang H, Basu A, Bernstein BE, Weitz DA. High-Throughput Single-Cell Labeling (Hi-SCL) for RNA-Seq Using Drop-Based Microfluidics. PLoS ONE 2015; 10:e0116328. PubMed
  • Yashiro-Ohtani Y, Wang H, Zang C, Arnett KL, Bailis W, Ho Y, Knoechel B, Lanauze C, Louis L, Forsyth KS, Chen S, Chung Y, Schug J, Blobel GA, Liebhaber SA, Bernstein BE, Blacklow SC, Liu XS, Aster JC, Pear WS. Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia. Proc Natl Acad Sci U S A 2014; 111:E4946-53. PubMed
  • Riggi N, Knoechel B, Gillespie SM, Rheinbay E, Boulay G, Suvà ML, Rossetti NE, Boonseng WE, Oksuz O, Cook EB, Formey A, Patel A, Gymrek M, Thapar V, Deshpande V, Ting DT, Hornicek FJ, Nielsen GP, Stamenkovic I, Aryee MJ, Bernstein BE, Rivera MN. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 2014; 26:668-81. PubMed
  • Stoeck A, Lejnine S, Truong A, Pan L, Wang H, Zang C, Yuan J, Ware C, MacLean J, Garrett-Engele PW, Kluk M, Laskey J, Haines BB, Moskaluk C, Zawel L, Fawell S, Gilliland G, Zhang T, Kremer BE, Knoechel B, Bernstein BE, Pear WS, Liu XS, Aster JC, Sathyanarayanan S. Discovery of Biomarkers Predictive of GSI Response in Triple-Negative Breast Cancer and Adenoid Cystic Carcinoma. 2014; 4:1154-67. PubMed
  • Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJ. Comparative analysis of metazoan chromatin organization. Nature 2014; 512:449-52. PubMed
  • Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos J, Weng Z, White KP, Hardison RC. Reply to Brunet and Doolittle: Both selected effect and causal role elements can influence human biology and disease. Proc Natl Acad Sci U S A 2014; 111:E3366. PubMed
  • Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suvà ML, Regev A, Bernstein BE. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014. PubMed
  • Attanasio C, Nord AS, Zhu Y, Blow MJ, Biddie SC, Mendenhall EM, Dixon J, Wright C, Hosseini R, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Afzal V, Ren B, Bernstein BE, Rubin EM, Visel A, Pennacchio LA. Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis. Genome Res 2014. PubMed
  • Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 2014; 157:580-94. PubMed
  • Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos JA, Weng Z, White KP, Hardison RC. Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A 2014. PubMed
  • Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet 2014; 46:364-70. PubMed
  • Mendenhall EM, Williamson KE, Reyon D, Zou JY, Ram O, Joung JK, Bernstein BE. Locus-specific editing of histone modifications at endogenous enhancers. Nat Biotechnol 2013; 31:1133-6. PubMed
  • Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, Ho QH, Sander JD, Reyon D, Bernstein BE, Costello JF, Wilkinson MF, Joung JK. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat Biotechnol 2013; 31:1137-42. PubMed
  • Abdel-Wahab O, Gao J, Adli M, Dey A, Trimarchi T, Chung YR, Kuscu C, Hricik T, Ndiaye-Lobry D, Lafave LM, Koche R, Shih AH, Guryanova OA, Kim E, Li S, Pandey S, Shin JY, Telis L, Liu J, Bhatt PK, Monette S, Zhao X, Mason CE, Park CY, Bernstein BE, Aifantis I, Levine RL. Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J Exp Med 2013; 210:2641-59. PubMed
  • Sander JD, Ramirez CL, Linder SJ, Pattanayak V, Shoresh N, Ku M, Foden JA, Reyon D, Bernstein BE, Liu DR, Joung JK. In silico abstraction of zinc finger nuclease cleavage profiles reveals an expanded landscape of off-target sites. Nucleic Acids Res 2013; 41:e181. PubMed
  • Isono K, Endo TA, Ku M, Yamada D, Suzuki R, Sharif J, Ishikura T, Toyoda T, Bernstein BE, Koseki H. SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing. Dev Cell 2013; 26:565-77. PubMed
  • Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT, Kohlbacher O, De Jager PL, Rosen ED, Bennett DA, Bernstein BE, Gnirke A, Meissner A. Charting a dynamic DNA methylation landscape of the human genome. Nature 2013; 500:477-81. PubMed
  • Rheinbay E, Suvà ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, Oksuz O, Rabkin SD, Martuza RL, Rivera MN, Louis DN, Kasif S, Chi AS, Bernstein BE. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep 2013; 3:1567-79. PubMed
  • Suvà ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science 2013; 339:1567-70. PubMed
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